The long-term goal of this project is to fully define the role of hemorheology in the pathogenesis of cerebral ischemia. We wish to investigate patients with subarachnoid hemorrhage in order to define hemorheological abnormalities related to cerebral ischemia. We also wish to determine the relationship between hemorheology, thrombosis, and ischemic symptoms with respect to carotid artery atherosclerotic plaques. We will investigate approximately 150 patients with subarachnoid hemorrhage over a period of five years. Hemorheological factors will be determined during their preoperative period and following discharge. Hemorheological determinations will include viscosity (whole blood, RBC-plasma suspension, and plasma) by cone-plate and couette viscometer; red cell aggregation measured by zeta sedimentation ratio and aggregation index; and red cell deformability using a new computerized filtration device. These hemorheological factors will be evaluated in the following contexts: 1) Clinical, as determined by repeated neurological evaluations; 2) Arteriographic, as determined by the presence of vasospasm; 3) Hydrocephalus, as determined by CT scan; 4) Platelete activation and other elements of the coagulation system, as determined by measurements of plasma beta-thromboglobulin, along with fibrinopeptides A and B, plasminogen, alpha 2- antiplasmin, and tissue plasminogen activator inhibitor; 5) Blood volume status, as measured by the chromium-51 method; and 6) Deep vein thrombosis, as determined clinically and by I-125 fibrinogen scans of the extremities. We will analyze approximately 350 carotid endarterectomy specimens over a five year period. The relationship between hemorheology factors and thrombotic activity on the carotid plaque surface will be evaluated using immunoperoxidase stains for fibrin and for beta-thromboglobulin. Regions of plaques subjected to high-and low-shear stress will be identified by pathologic and arteriographic analysis. The immunohistologic characteristics of carotid artery atherosclerotic plaques will be examined in the context of these rheologic features. In addition, pathological features of the carotid plaques will be analyzed with respect to abnormalities of clinical hemorheology (e.g., viscosity and red cell aggregation) and coagulation. Finally, we will examine the relationship between these hemorheological and pathologic features and the presence of ischemic symptoms related to carotid artery disease.